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WO2013147649A2 - Inhibiteurs de la voie de signalisation pi3k/akt/ikk/nf-kb, leurs sels pharmaceutiquement acceptables et compositions les comprenant pour la prévention et le traitement de maladies virales - Google Patents

Inhibiteurs de la voie de signalisation pi3k/akt/ikk/nf-kb, leurs sels pharmaceutiquement acceptables et compositions les comprenant pour la prévention et le traitement de maladies virales Download PDF

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Publication number
WO2013147649A2
WO2013147649A2 PCT/RU2013/000243 RU2013000243W WO2013147649A2 WO 2013147649 A2 WO2013147649 A2 WO 2013147649A2 RU 2013000243 W RU2013000243 W RU 2013000243W WO 2013147649 A2 WO2013147649 A2 WO 2013147649A2
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Prior art keywords
methyl
amino
phenyl
benzo
pyrimidin
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PCT/RU2013/000243
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English (en)
Russian (ru)
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WO2013147649A3 (fr
Inventor
Петр Олегович ФЕДИЧЕВ
Андрей Александрович ВИННИК
Original Assignee
ХОЛИН, Максим Николаевич
НЕСТЕРУК, Владимир Викторович
Открытое Акционерное Общество "Валента Фармацевтика"
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Publication of WO2013147649A2 publication Critical patent/WO2013147649A2/fr
Publication of WO2013147649A3 publication Critical patent/WO2013147649A3/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses

Definitions

  • PI3K / AKT / IKK / NF-kV signaling pathway inhibitors their pharmaceutically acceptable salts and compositions containing them for the prevention and treatment of viral diseases
  • This invention relates to the field of prevention and treatment of viral diseases, namely, the use of PI3K / AKT / IKK / NF-kB signaling pathway inhibitors, their pharmaceutically acceptable salts, and pharmaceutical compositions and dosage forms containing them for the prevention and treatment of viral diseases.
  • PI3K / AKT / IKK / NF-kB signaling pathway inhibitors their pharmaceutically acceptable salts, and pharmaceutical compositions and dosage forms containing them for the prevention and treatment of viral diseases.
  • IKK PI3K / AKTAKK / NF-kB - IkappaB kinase inhibitors
  • Patent application US2011268722 (WO2011133879) describes combined antitumor preparations containing PI3K / AKT / IKX / NF-kB signaling pathway inhibitors.
  • US20060025419 describes the use of PI3K / AKT / IKK / NF-kB signaling pathway inhibitors for the treatment of melanoma, and US20100249142 for the treatment of a number of oncological diseases.
  • the use of PI3K / AKTAKK / NF-kB signaling pathway inhibitors for monitoring the effects of immunomodulators (US2011111417), local anesthesia (US2010159015), treatment of diseases of the nervous system (US2005075341), as immunomodulators (EP2010537), etc. is also described.
  • immunomodulators US201111141-7
  • US2010159015 local anesthesia
  • treatment of diseases of the nervous system US2005075341
  • EP2010537 immunomodulators
  • P13K / AKTLKK / YB-kV published information on their use in the treatment of viral diseases, for example:
  • IKK is understood to mean IkB kinase, an enzymatic complex that is involved in the cellular response to inflammation and is located in the PI3K / AKTAK 7NF-kB signaling cascade.
  • the present invention relates to the use of PI3K / AKTAKK / NF-kB signaling pathway inhibitors, their pharmaceutically acceptable salts, and pharmaceutical compositions and dosage forms containing them for the prevention and / or treatment of various viral diseases.
  • the present invention provides a PI3K / Akt / IKK / Nf-kB signaling pathway inhibitor, or a pharmaceutically acceptable salt thereof, for the prevention and / or treatment of at least one disease from Table 1.
  • the present invention provides a pharmaceutical composition for the prophylaxis and / or treatment of at least one disease from Table 1, comprising at least one PI3K7Ak ⁇ KK / Nf-kB signaling pathway inhibitor or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, excipient or diluent. 3.
  • the present invention provides a dosage form for the prophylaxis and / or treatment of at least one disease from Table 1, comprising a PI3K / Akt / IK / Nf-kB signaling pathway inhibitor or a pharmaceutically acceptable salt thereof.
  • the present invention provides an IKK inhibitor or a pharmaceutically acceptable salt thereof for the prevention and / or treatment of at least one disease from Table 1.
  • the present invention provides a pharmaceutical composition for the prophylaxis and / or treatment of at least one disease from Table 1, comprising an IKK inhibitor or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, excipient or diluent. 6. In another embodiment, the present invention provides a dosage form for the prevention and / or treatment of at least one disease from table 1, containing an IKK inhibitor or a pharmaceutically acceptable salt thereof.
  • the present invention provides at least one compound from Table 2, or a pharmaceutically acceptable salt thereof, for the prevention and / or treatment of at least one disease from Table 1.
  • the present invention provides an analogue of at least one of the compounds from table 2 or its pharmaceutically acceptable salt, for the prevention and / or treatment of at least one disease from table 1.
  • the present invention provides a pharmaceutical composition for the prophylaxis and / or treatment of at least one disease of Table 1, comprising at least one of the compounds of Table 2, or a pharmaceutically acceptable salt thereof, and at least one a pharmaceutically acceptable carrier, excipient or diluent.
  • the present invention provides a dosage form comprising at least one of the compounds of Table 2 or a pharmaceutically acceptable salt thereof for the prevention and / or treatment of at least one disease of Table 1.
  • the present invention provides a medicament for the prevention and / or treatment of at least one of the diseases of Table 1, comprising in a therapeutically effective amount of at least one of the compounds of Table 2 or a pharmaceutically acceptable salt thereof.
  • the present invention provides a compound 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1, 2-a] quinoxaline
  • the present invention provides the use of at least one compound of Table 2 or a pharmaceutically acceptable salt thereof for the prevention and / or treatment of viral diseases.
  • the present invention provides a compound 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1, 2-a] quinoxaline
  • the present invention provides a compound 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1, 2-a] quinoxaline
  • the present invention provides a pharmaceutical composition for the prophylaxis and / or treatment of type A influenza, comprising 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1, 2-a] quinoxaline
  • the present invention provides at least one compound from table 2 or its pharmaceutically acceptable salt used (used) for the prevention and / or treatment of at least one of the diseases from table 1. 17.
  • the present invention provides a method for the prevention and / or treatment of at least one disease from table 1 person and / or an animal by administering to such a person and / or animal in a therapeutically effective amount of at least one PI3K7AktAKK / Nf-kB inhibitor of the signaling pathway or a pharmaceutically acceptable salt thereof.
  • the present invention provides a method of preventing and / or treating at least one disease from a human and / or animal table 1 by administering to such a person and / or animal a therapeutically effective amount of at least one IKK inhibitor or a pharmaceutically acceptable salt.
  • the present invention provides a method for preventing and / or treating at least at least one disease from table 1 of a person and / or animal by administering to such a person and / or animal in a therapeutically effective amount of at least one compound from table 2 or a pharmaceutically acceptable salt thereof.
  • the present invention provides a method for the prevention and / or treatment of influenza and / or SARS by administering to such a person and / or animal 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1,2- a] quinoxaline
  • the present invention provides a method for preventing and / or treating at least one disease from a human and / or animal table 1 by administering to such a person and / or animal a therapeutically effective amount of a pharmaceutical composition comprising at least one compound of Table 2 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, excipient or diluent.
  • the present invention provides a method for preventing and / or treating at least one disease from a human and / or animal table 1 by administering to such a person and / or animal in a therapeutically effective amount of a pharmaceutical composition comprising at least one PI3K / Akt / IKJ / Nf-kB inhibitor of the signaling pathway or its pharmacologically acceptable salt or one IKK inhibitor or its pharmaceutically acceptable salt or at least one compound from table 2 or its pharmaceutics Eski acceptable salt thereof, and at least one pharmaceutically acceptable carrier, excipient or diluent, and at least one other drug or an antiviral drug or compound from table 3. 23.
  • the present invention provides a pharmaceutical composition for preventing and / or treating at least one disease from a human and / or animal table 1, comprising at least one PI3K / Akt / IKK / Nf-kB signaling inhibitor the pathway or its pharmacologically acceptable salt or at least one IKK inhibitor or its pharmaceutically acceptable salt or at least one compound from table 2 or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable nose an agent, excipient or diluent, in combination with at least one other drug or antiviral drug or drug used to prevent and / or treat at least one disease indicated in table 1, for example, but not limited to at least one compound or the drug from table 3.
  • the present invention provides at least one signaling pathway inhibitor PBK / Akt / IKK / Nf-kB, an IKK inhibitor or a compound of Table 2 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for prophylaxis and / or treating at least one disease indicated in table 1.
  • the present invention provides at least one PI3K / Akt / IKK / Nf-kB signaling pathway inhibitor, an IKK inhibitor, or a compound of Table 2, or a pharmaceutically acceptable salt thereof, together with at least one other drug used for prophylaxis and / or treatment of at least one disease indicated in table 1, including at least one compound from table 3, for the manufacture of a combination drug for the prevention and / or treatment of at least one disease Table 1.
  • a solvate or solvate of a salt thereof or a salt adduct thereof or a complex salt thereof thereof is used physiologically a functional derivative or its analogue or its stereoisomer or its prodrug.
  • the solvate or solvate of its salt or its salt adduct or its complex salt is used as the biologically active substance.
  • At least one other disease is associated with at least one virus indicated in table 1.
  • EFFECT obtaining / invention of a new biologically active compound, including those indicated in table 2, which can be used to prevent and / or treat and / or alleviate the symptoms and consequences of at least one disease indicated in table 1 (compounds in regarding which previously there was no information about the possibility of its use in the treatment of the corresponding disease), new methods of treating such diseases, new pharmaceutical compositions and combinations for the treatment of these diseases knowledge, the new use of the above substances for the treatment of the above diseases, as well as for the production of medicines for the treatment of the above diseases.
  • the compounds listed in table 1 and methods for their preparation are known in the art. Many of the molecules described in Table 2 are already manufactured commercially. Thus, the inventions described in this application have industrial applicability.
  • patch can be either a dosage or non-dosage form
  • Dosage forms of the present invention can be of various state of aggregation
  • Hard tablets, powders, capsules, dragees, granules, caramel, medicinal pencil
  • Liquid solutions, tinctures, suspensions, emulsions, drops, syrups, medicines
  • the present invention also relates to any pharmaceutically acceptable carrier that assists in the delivery to the body as an active substance.
  • any pharmaceutically acceptable carrier that assists in the delivery to the body as an active substance.
  • compositions of the dosage forms any examples of compositions and / or dosage forms commonly used for systemically used drugs can be given.
  • compositions for the purpose of making a variant of the pharmaceutical composition of the present invention, but not limited to these examples, an effective amount of a substance from the class described or covered by this application or its salt can be taken.
  • a pharmaceutically acceptable carrier vehicle
  • the carriers can be a wide variety of forms and substances depending on the composition that is intended to be administered to the patient. It is more convenient that these pharmaceutical compositions be in standardized doses, for example, for oral administration or parenteral administration.
  • the carrier may be sterile water, saline, or other ingredients, for example, substances that improve solubility.
  • the carrier may consist of physiological or saline solution, glucose solution, or a mixture of saline and glucose solution, buffer.
  • injectable suspensions they may also be prepared in a representative or representatives of liquid carriers, dispersing agents and similar substances and compositions suitable for each specific case or series of cases.
  • a therapeutically active agent as described herein or coated with it, in the form of a powder, which is intended to be converted shortly before administration into a liquid form.
  • the pharmaceutical composition may also contain various other ingredients known in the art, such as stabilizing agents, lubricant, buffer, emulsifier, viscosity and / or tackifier, any surfactant, preservative, antioxidant, colorant, other additives and the like.
  • stabilizing agents such as stabilizing agents, lubricant, buffer, emulsifier, viscosity and / or tackifier, any surfactant, preservative, antioxidant, colorant, other additives and the like.
  • the dosage in the description is used as a physically separate part, used for a single application. Such a portion contains a certain amount of the active ingredient necessary to obtain a therapeutic effect together with an acceptable pharmaceutical carrier.
  • Examples of such dosages are tablets of various shapes and appearance, capsules, powder sachets, lozenges, plates, suppositories, suppositories, injection solutions and so on, as well as various combinations of the above, but not limited to.
  • starch in an amount of 0.1 mg to 100 mg per tablet was used as a filler to give the best flowability and compressibility of the active substance.
  • Potato and / or modified starch may be used.
  • lubricants and glidants As lubricants and glidants, stearic acid, aerosil or collie don are used. These substances provide good flowability and uniform supply of tableted masses from the hopper into the matrix, and as a result gives higher accuracy and consistency in the dosage of the drug substance. Contribute to the easier ejection of tablets from the matrix, preventing the formation of scratches on their faces.
  • lactose in an amount of up to 60 mg can be added.
  • the result is a mixture of substances having good technological properties in the process of granulation and tableting.
  • the manufactured tablets have properties that meet the requirements of a pharmaceutical agent. They have a marketable appearance without chips and cracks, with the necessary strength and disintegration, and are stored for at least 2 years.
  • the new pharmaceutical formulation is in the form of a solid dosage form, preferably, but not necessarily, coated in the form of a tablet.
  • the presence of the shell of the claimed composition gives, firstly, the stability of the composition during storage, and secondly, improves its appearance and organoleptic properties.
  • a composition consisting of at least a PI3 / Akt / IKK / Nf-kB signaling pathway or IKK inhibitor or compound indicated in table 2 and at least one other drug used for the prevention and / or treatment of at least one disease indicated in table 1, for example, the compound or preparation of table 3, a synergistic effect is achieved.
  • Non-limiting examples of such a combination composition may include the following: a pharmaceutical composition comprising at least two formulations.
  • a pharmaceutical composition for treating influenza and / or acute respiratory viral infections caused by influenza virus containing 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1,2- a] quinoxaline in an amount of 0.1 mg to 100 mg and oseltamivir in an amount of 0.1 mg to 100 mg.
  • any or at least one compound from table 3 can be used in one composition with any or at least one compound from table 2, for the prevention and / or treatment of at least one disease indicated in table 1.
  • the effective dose for the active substances of this invention depends on the chosen route of administration, as well as on other factors, such as the age and weight of the patient, which are known to the attending physician.
  • the dosage also depends on the disease to be prevented and / or treated.
  • the daily dose for the prophylaxis and / or treatment of the diseases from Table 1 may range from 0.01 to 300 mg / kg of the weight of a patient who needs prophylaxis and / or treatment.
  • the active compounds of this invention can be administered from one to three times per day (i.e., from one to three doses per day) at a dose of about 0.01 to about 100 mg / kg of patient weight, although depending on the weight and the patient’s condition, the nature and severity of the disease that the patient suffers from, and especially the route of administration, it will be necessary to adjust this dose.
  • changes in dosage may occur depending on the characteristics of the patients to be treated and the individual response of the subject to the indicated drug, as well as the type of pharmaceutical composition selected, the period of use and the time interval during which such administration is carried out.
  • doses for the compound 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1,2-a] quinoxaline prevention and / or treatment of influenza and other diseases from table 1 - from 0.1 to 10 mg / kg , from 1 mg / kg to 200 mg / kg, from 0.1 mg / kg to 1 mg / kg, from 50 mg / kg to 200 mg / kg, from 25 mg / kg to 100 mg / kg.
  • non-limiting examples of the PI3K / Akt / IKK / Nf-kB signaling pathway inhibitors and / or IKK inhibitors used therein may be the compounds (at least one compound) shown in Table 2.
  • Non-limiting an example of such joint use can be the simultaneous administration of at least two drugs, one from table 2, the other from table 3.
  • 8-dimethylimidazole [1,2-a] quinoxaline in doses from 0.01 mg / kg body weight to 100 mg / kg body weight is applied 1, 2, 3 or 4 times a day at the same time or at intervals of up to 24 hours with oseltamivir in doses from 0.01 mg / kg body weight to 100 mg / kg body weight) for a period of up to 1 month.
  • children weighing less than 15 kg are prescribed 30 mg 2 times a day; children weighing 15-23 kg - 45 mg 2 times a day; children weighing 23-40 kg - 60 mg 2 times a day; children over 40 kg - 75 mg 2 times a day.
  • any compound from table 2 is used simultaneously with at least one compound or drug listed in table 3.
  • These same drugs can be used in different sequences, including, for example, the drug from table 3 - from 1 minute to 2 weeks after taking the drug from table 2 and vice versa - the drug from table 2 during the same time intervals after taking the drug from table 3. It is assumed both single and repeated use of both drugs simultaneously or one after d another - during any of the indicated periods in a different sequence.
  • the drug from table 2 is administered orally or by injection in the dose range from 0.01 to 100 mg / kg 1.2 or 3 times a day on the day of infection and the drug from table 3 is orally in the range doses from 0.01 to 100 mg / kg 1, 2 or 3 times a day for 1-60 days after infection with the virus from table 1 or for 1 day to 2 weeks, or 2 days to 3 weeks.
  • Example 1 Biological activity in vitro. The use of compounds for the treatment of virus agents can be demonstrated by the activity of the compounds from the table
  • the compounds are taken:
  • N ° 80 NF-KB Activation Inhibitor All compounds taken were dissolved in 100% DMSO, final concentration 4 mM. For experiments, concentrations of 10 and 1 ⁇ M were used, and the DMSO content was 0.25%. However, for compounds 60 (Ikk inhibitor VII) and 80 (NF- ⁇ activation inhibitor), additional acidification of the pH was required by the addition of HCl to achieve final concentrations of 20 and 3 ⁇ M, respectively.
  • influenza-induced cytopathic effect was examined on a culture of MDCK cells (Madin-Darby canine kidney) by infecting them with the influenza A virus subtype FM1.
  • Cells were infected in the presence of 10 ⁇ g / ml trypsin in DMEM and test substances at a concentration of 10 and 1 ⁇ M (three repetitions for each concentration).
  • Oseltamivir (Tamiflu) at a concentration of 100 ⁇ M was used as a control.
  • uninfected cells were incubated in the presence of the same concentrations of compounds. After a 5-day incubation period, the plates were processed to detect live cells (using the resazurin method). Virus inhibition and cytotoxicity (cell death caused by test compounds in the absence of viral infections) are expressed as a percentage. Cell morphology was monitored by visual inspection during the experiment.
  • Example 2 In-vivo biological activity
  • the effectiveness of PI3K / Akt / IKK / Nf-kB inhibitors of the signaling pathway, for example, but not limited to, compounds of Table 2 or IKK inhibitors for the purposes of the present invention can be confirmed by the example of a number of PI3K7Ak1 [KK / Nf-kB inhibitors the signaling pathway, which are inhibitors of IKK, in relation to the experimental form of influenza A in white mice intranasally infected with the influenza virus, strains A / Aichi / 2/68 (H3N2).
  • the work can be used influenza virus, strain A / Aichi / 2/68 (H3N2), adapted to the lungs of white mice.
  • white mice weighing 10-12 g can be used.
  • 20 animals are used. Additionally, 20 animals are included to control the toxicity of the compound at its maximum dose, 20 animals (herd control - saline solution) and 20 animals (infected untreated group). For control the antiviral activity is a group treated with Tamiflu - 20 animals.
  • mice 120 mice (6 groups of 20 animals each) are required.
  • a virus-containing suspension is injected into both nostrils of white mice under light ether anesthesia in a volume of 50 ⁇ l.
  • the infectious dose is 10 to 30 LD50 of the A / Aichi / 2/68 influenza virus (H3N2) for 20 mice in each group. Observation of animals is carried out within 14 days from the moment of infection, recording their death.
  • Oseltamivir brand name Tamiflu®
  • remantadine remantadine
  • arbidol remantadine
  • others can be used as comparison preparations. These samples exhibit protective activity in the described experiment.
  • composition mg per tablet:
  • compositions 3.2 examples of compositions 3.2.
  • composition mg per tablet:
  • the table contains the name of the viruses and a non-limiting list of examples of diseases associated with the corresponding virus.
  • Adenovirus is a type of acute respiratory viral infection (SARS), SARS associated with adenovirus or caused by adenovirus, adenovirus infection
  • SARS acute respiratory viral infection
  • SARS associated with adenovirus or caused by adenovirus adenovirus infection
  • Epstein - Epstein - Barr for example, but not Barr, VEB limited to
  • Infectious mononucleosis multiglandular adenosis, glandular fever, Filatov’s disease
  • Lymphogranulomatosis Lymphogranulomatosis
  • Burkitt Burkitt
  • Some of non-Hodgkin’s lymphomas Nasopharyngeal carcinoma (nasopharyngeal cancer), General variability, Variable
  • Herpetic tonsillitis (herpangina)
  • Flaviviruses dengue fever, fever
  • Influenza A virus acute respiratory viral (influenza virus serotype of infection (SARS), influenza, influenza A, type A influenza virus, diseases
  • subtype A associated with influenza viruses
  • ARVI Respiratory acute respiratory syncytial virus viral infections
  • Rhinovirus for example, but not acute respiratory confining to type viral infections (ARVI), 2.16.39) rhinovirus infections
  • Adeno-associated diseases and conditions the virus associated with or caused by the virus.
  • Taxotere Docetaxel
  • Taxotere Docetaxel
  • Trp-Glu-Lys-Phe-OH Akt Inhibitor VIII Isozyme-Selective, Akti-1/2 l, 3-Dihydro-l- (l - ((4- (6-phenyl-lH-imidazo [4,5-g] quinoxalin-7-yl) phenyl ) methyl) -4- piperidinyl) -2H- benzimidazol-2-one,
  • composition comprising at least two drugs.
  • composition for treatment influenza and / or SARS caused by influenza virus containing 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1, 2-a] quinoxaline weighing from 0.1 mg to 100 mg and oseltamivir weighing from 0.1 mg up to 100 mg, any compound from table 2 applies
  • Adenovirus acute bacterial species Adenovirus acute bacterial species
  • ARVI ARVI
  • ARVI recombinant, associated with human
  • adenovirus or (IgaZym) adenovirus or (IgaZym)
  • adenovirus (Ribavirin BEND A); adenovirus acetylcysteine
  • VZ Menengitis virus, myocarditis, (Picovir) and others.
  • Epstein associated with (EPB348, MIV606) Barr, EBV Epstein virus — and others.
  • Lymphogranulomatosis Hodgkin's disease
  • Burkitt's lymphoma Central African lymphoma
  • Hepatitis B virus hepatitis B Entecavir Teviral
  • Hepatitis B virus hepatitis C ribavirin (Viranis,
  • telaprevir Incivek
  • Victrelis and others.
  • HIV virus HIV virus, AIDS Ritonavir (Norvir); efavirenz immunodeficiency (human Adco-a, Efavirenz);
  • human papillomavirus type 6 L1 (recombinant) (Gardasil) and others.
  • H1N1 influenza viruses (zanamivir)
  • Pentanedioic acid imidazolylethanamide e.g.
  • Kaposi paclitaxel Panataxel
  • Myxoma virus myxomatosis Attenuated strain of MICS-98 rabbit myxoma virus and others.
  • Poliovirus polio poliovirus type 1 Poliovirus polio poliovirus type 1
  • poliovirus type 1 inactivated
  • poliovirus type 2 inactivated
  • poliovirus type 3 inactivated
  • the invention is applicable in the field of prevention and treatment of viral diseases, namely, in the use of PBK / AKT / IKK / NF-KB signaling pathway inhibitors, their pharmaceutically acceptable salts, and pharmaceutical compositions and dosage forms containing them for the prevention and treatment of viral diseases .

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Abstract

L'invention concerne des inhibiteurs de la voie de signalisation PI3K/AKT/IKK/NF-kB, leurs analogues et leurs sels pharmaceutiquement acceptables et des compositions pharmaceutiques les comprenant pour la prévention et le traitement de maladies virales. L'invention est liée à des méthodes de prévention et de traitement de maladies virales utilisant des inhibiteurs de la voie de signalisation PI3K/AKT/IKK/NF-kB, leurs analogues et leurs sels pharmaceutiquement acceptables et les compositions pharmaceutiques les comprenant pour la prévention de maladies virales et la fabrication de médicaments.
PCT/RU2013/000243 2012-03-29 2013-03-25 Inhibiteurs de la voie de signalisation pi3k/akt/ikk/nf-kb, leurs sels pharmaceutiquement acceptables et compositions les comprenant pour la prévention et le traitement de maladies virales WO2013147649A2 (fr)

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RU2012112128 2012-03-29
RU2012112128/15A RU2012112128A (ru) 2012-03-29 2012-03-29 ИНГИБИТОРЫ СИГНАЛЬНОГО ПУТИ PI3K/AKT/IKK/NF-kB, ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ И СОДЕРЖАЩИЕ ИХ КОМПОЗИЦИИ ДЛЯ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ ВИРУСНЫХ ЗАБОЛЕВАНИЙ

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Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015001491A1 (fr) 2013-07-02 2015-01-08 Rhizen Pharmaceuticals Sa Inhibiteurs de protéine kinase pi3k, en particulier inhibiteurs delta et/ou gamma
WO2016069854A1 (fr) * 2014-10-30 2016-05-06 Virginia Commonwealth University Amélioration des effets anti-tumoraux, anti-viraux et anti-protozoaires du 2-amino-n-[4-[5-phénanthrén-2-yl-3-(trifluorométhyl)pyrazol-1-yl] phényl]acétamide (osu-03012) et d'autres médicaments pharmaceutiques
CN110859839A (zh) * 2018-08-27 2020-03-06 中国人民解放军军事科学院军事医学研究院 噻唑烷二酮类化合物在制备抗腺病毒药物中的应用
CN111269231A (zh) * 2018-12-04 2020-06-12 安徽中科拓苒药物科学研究有限公司 一种选择性PI3Kδ抑制剂及其用途
CN111793113A (zh) * 2019-04-07 2020-10-20 首都医科大学 二羟甲基四氢咔啉-3-甲酰-The-HGK其合成,活性和应用
US11000491B2 (en) 2017-05-05 2021-05-11 Hepanova, Inc. Amino-aryl-benzamide compounds and methods of use thereof
CN113045559A (zh) * 2021-03-15 2021-06-29 贵州医科大学 一种二芳基脲类PI3Kα/mTOR双靶点抑制剂及其药物组合物和应用
WO2021160109A1 (fr) * 2020-02-13 2021-08-19 劲方医药科技(上海)有限公司 Composé de dihydronaphtyridinone, son procédé de préparation et son utilisation médicale
CN113332290A (zh) * 2021-05-11 2021-09-03 湖北工业大学 Voxtalisib化合物在制备抗EV71病毒药物中的应用
WO2022029639A1 (fr) * 2020-08-07 2022-02-10 Berlin-Chemie Ag Formulations pharmaceutiques améliorées comprenant des inhibiteurs de pi3k
WO2022106579A1 (fr) * 2020-11-20 2022-05-27 Institut National De La Sante Et De La Recherche Medicale (Inserm) Composés pour traiter une maladie associée à la sénescence des macrophages
WO2023170187A1 (fr) * 2022-03-09 2023-09-14 Technische Universität München INHIBITION DE L'ABSORPTION DE PATHOGÈNES INTRACELLULAIRES PAR DES INHIBITEURS DU COMPLEXE IKK-α/NIK
RU2809869C1 (ru) * 2020-02-13 2023-12-19 Генфлит Терапьютикс (Шанхай) Инк. Соединение на основе дигидронафтиридинона, и способ его получения, и его применение в медицине

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WO2015001491A1 (fr) 2013-07-02 2015-01-08 Rhizen Pharmaceuticals Sa Inhibiteurs de protéine kinase pi3k, en particulier inhibiteurs delta et/ou gamma
WO2016069854A1 (fr) * 2014-10-30 2016-05-06 Virginia Commonwealth University Amélioration des effets anti-tumoraux, anti-viraux et anti-protozoaires du 2-amino-n-[4-[5-phénanthrén-2-yl-3-(trifluorométhyl)pyrazol-1-yl] phényl]acétamide (osu-03012) et d'autres médicaments pharmaceutiques
US12053443B2 (en) 2017-05-05 2024-08-06 Hepanova, Inc. Amino-aryl-benzamide compounds and methods of use thereof
US11000491B2 (en) 2017-05-05 2021-05-11 Hepanova, Inc. Amino-aryl-benzamide compounds and methods of use thereof
CN110859839A (zh) * 2018-08-27 2020-03-06 中国人民解放军军事科学院军事医学研究院 噻唑烷二酮类化合物在制备抗腺病毒药物中的应用
CN110859839B (zh) * 2018-08-27 2023-04-18 中国人民解放军军事科学院军事医学研究院 噻唑烷二酮类化合物在制备抗腺病毒药物中的应用
CN111269231A (zh) * 2018-12-04 2020-06-12 安徽中科拓苒药物科学研究有限公司 一种选择性PI3Kδ抑制剂及其用途
CN111269231B (zh) * 2018-12-04 2023-06-09 安徽中科拓苒药物科学研究有限公司 一种选择性PI3Kδ抑制剂及其用途
CN111793113A (zh) * 2019-04-07 2020-10-20 首都医科大学 二羟甲基四氢咔啉-3-甲酰-The-HGK其合成,活性和应用
CN111793113B (zh) * 2019-04-07 2022-08-05 首都医科大学 二羟甲基四氢咔啉-3-甲酰-The-HGK其合成,活性和应用
WO2021160109A1 (fr) * 2020-02-13 2021-08-19 劲方医药科技(上海)有限公司 Composé de dihydronaphtyridinone, son procédé de préparation et son utilisation médicale
CN115135648B (zh) * 2020-02-13 2024-02-09 劲方医药科技(上海)有限公司 二氢萘啶酮类化合物，其制法与医药上的用途
CN115135648A (zh) * 2020-02-13 2022-09-30 劲方医药科技(上海)有限公司 二氢萘啶酮类化合物，其制法与医药上的用途
RU2809869C1 (ru) * 2020-02-13 2023-12-19 Генфлит Терапьютикс (Шанхай) Инк. Соединение на основе дигидронафтиридинона, и способ его получения, и его применение в медицине
WO2022029639A1 (fr) * 2020-08-07 2022-02-10 Berlin-Chemie Ag Formulations pharmaceutiques améliorées comprenant des inhibiteurs de pi3k
WO2022106579A1 (fr) * 2020-11-20 2022-05-27 Institut National De La Sante Et De La Recherche Medicale (Inserm) Composés pour traiter une maladie associée à la sénescence des macrophages
CN113045559A (zh) * 2021-03-15 2021-06-29 贵州医科大学 一种二芳基脲类PI3Kα/mTOR双靶点抑制剂及其药物组合物和应用
CN113332290B (zh) * 2021-05-11 2023-09-15 湖北工业大学 Voxtalisib化合物在制备抗EV71病毒药物中的应用
CN113332290A (zh) * 2021-05-11 2021-09-03 湖北工业大学 Voxtalisib化合物在制备抗EV71病毒药物中的应用
WO2023170187A1 (fr) * 2022-03-09 2023-09-14 Technische Universität München INHIBITION DE L'ABSORPTION DE PATHOGÈNES INTRACELLULAIRES PAR DES INHIBITEURS DU COMPLEXE IKK-α/NIK

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